The dexamethasone‐suppressed corticotropin‐releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo‐Cushing's states

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Abstract
Objective Cushing's syndrome (CS), when fully expressed, is easily diagnosed. Mild cases, however, may require careful distinction from pseudo‐Cushing's states as may occur in depression, alcoholism, polycystic ovary disease and visceral obesity. The aim of the present study is a reappraisal of the diagnostic accuracy of the two tests most commonly used to differentiate CS from pseudo‐Cushing's: corticotropin‐releasing hormone (CRH) stimulation after low dose dexamethasone administration and desmopressin stimulation. Design The study population comprised 32 patients with CS and 23 with pseudo‐Cushing's evaluated retrospectively. Methods Urinary free cortisol (UFC), serum cortisol at midnight and after low dose dexamethasone (1 mg overnight and 2 mg over two days) were measured. Further, patients were tested with dexamethasone + CRH and desmopressin and the diagnostic performances of the two tests were compared in the entire series as well as in patients with mild hypercortisolism only (i.e. UFC < 690 nmol/24 h). Results As expected, measurement of UFC, assessment of cortisol rhythmicity and inhibition after 1 mg/2 mg dexamethasone failed to clearly classify patients with pseudo‐Cushing's. Administration of CRH following 2‐mg dexamethasone achieved 100% sensitivity but 62·5% specificity. Conversely, desmopressin testing correctly classified all but two patients with pseudo‐Cushing's (90% specificity) with 81·5% sensitivity. Diagnostic accuracy was comparable in the subgroup with mild hypercortisolism (21 CS, all 23 pseudo‐Cushing's patients). Desmopressin offered an incremental diagnostic effectiveness of 35·8/million inhabitants compared with dexamethasone + CRH as a second‐line test. Conclusions Neither of the two tests guarantees absolute diagnostic accuracy. The specificity of dexamethasone + CRH is less brilliant than previously reported and appears to be inferior to desmopressin stimulation. The greatest diagnostic effectiveness results from the low‐dose dexamethasone test combined with the desmopressin test. Skilful use of dynamic testing and balanced clinical judgement are necessary to distinguish between Cushing's syndrome and pseudo‐Cushing's.